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Pelizaeus-Merzbacher Disease: Causes, Types, Diagnosis and Treatment

Published on Jan 31, 2023   -  5 min read


A rare genetic condition called Pelizaeus-Merzbacher disease affects the central nervous system. Read the article below to learn more.

What Is Pelizaeus-Merzbacher Disease?

An uncommon, progressive, degenerative condition of the central nervous system called Pelizaeus-Merzbacher disease (PMD) causes a decline in motor control, cognitive function, and coordination. The condition belongs to a class of genetic illnesses called leukodystrophies that disrupt the development of the fatty coating known as the myelin sheath, which surrounds and shields the nerve fibers in the brain. Myelin's insulation of nerve fibers facilitates the quick transmission of nerve impulses.

Particularly in Pelizaeus-Merzbacher illness, the nervous system's capacity to generate myelin is diminished due to hypomyelination, and overall neurological function is consequently compromised. The disease is brought on by a mutation in the proteolipid protein-1 gene (PLP1), which regulates the production of a myelin protein. Males with Pelizaeus-Merzbacher disease and mothers who carry the PLP1 mutation inherit the condition as an X-linked recessive characteristic. The central nervous system disorder Pelizaeus-Merzbacher disease mostly affects men.

What Causes Pelizaeus-Merzbacher Disease?

Proteolipid-protein-1 gene mutations result in Pelizaeus-Merzbacher disease. Between five and 20 percent of those who have Pelizaeus-Merzbacher disease are thought to be devoid of known PLP1 gene mutations. In some situations, the condition's cause is not known. The PLP1 gene usually experiences a change (mutation), which leads to Pelizaeus-Merzbacher disease. This gene mutation can be inherited from one or both parents.

Proteolipid protein 1 and its modified variant, DM20, are produced using instructions from the PLP1 gene. The central nervous system's proteolipid protein 1 is mostly present in nerves, and the nerves that connect the brain, spinal cord, and muscles create the majority of DM20. The majority of myelin is made up of these two proteins, which tie it to the nerve cells and are present in the cell membranes of nerve cells.

The PLP1 gene is copied by the majority of Pelizaeus-Merzbacher illness mutations, which increases the production of DM20 and proteolipid protein 1. Other mutations cause the synthesis of aberrant, frequently misfolded proteins. Proteins that are too many or abnormally shaped get caught inside the cell structures and are unable to reach the cell membrane. Proteolipid protein 1 and DM20 are consequently unavailable for myelin formation. Protein buildup causes edema and the degeneration of nerve fibers. Other mutations result in the deletion of the PLP1 gene, which stops the creation of the proteins DM20 and proteolipid protein 1, which leaves the cell membrane devoid of these proteins and makes whatever myelin that does develop unstable and easily degradable.

What Are the Types of Pelizaeus-Merzbacher Disease?

There are two forms of Pelizaeus-Merzbacher disease: classic and connatal. These two categories can overlap in features despite having varying degrees of severity.

  • Classic Pelizaeus-Merzbacher: The more typical form of the disease is the Classic Pelizaeus-Merzbacher. People with the classic Pelizaeus-Merzbacher disease often have hypotonia (poor muscle tone), nystagmus (uncontrollable eye movements), and delayed development of motor abilities, such as sitting or grasping things, within the first year of life. Some people can walk with a little assistance. Despite these neurological issues, children improve their cognitive and physical skills throughout childhood. Nevertheless, development often ends around the time of puberty, and these talents are gradually lost (developmental regression). Nystagmus typically disappears as the illness develops, but other movement abnormalities include muscle stiffness (spasticity), issues with movement and balance (ataxia), head and neck tremors (titubation), involuntary muscle tensing (dystonia), and jerking (choreiform) motions also start to appear.

  • Connatal Pelizaeus-Merzbacher: This disease is the most severe. Feeding issues, sluggish weight gain and growth, high-pitched breathing due to airway obstruction (stridor), nystagmus, progressive speech difficulties (dysarthria), severe ataxia, hypotonia, and seizures are all symptoms that can start in infancy. Affected children experience spasticity, which causes joint abnormalities (contractures) that limit movement as the condition develops. Connatal Pelizaeus-Merzbacher disease patients are unable to walk, and many cannot use their arms on purpose. They also struggle with language expression; however, they can typically interpret speech (receptive language).

What Are the Signs and Symptoms of the Pelizaeus-Merzbacher Disease?

Pelizaeus-Merzbacher’s disease typically manifests in the first few months of life. Nystagmus (rapid, involuntary, rhythmic eye motion) and poor muscular tone are the most distinctive early symptoms. Depending on the mutation's severity, motor skills either develop slowly or never at all. Children with Pelizaeus-Merzbacher disease typically develop language skills and can speak to some extent. Other symptoms involve:

  • Little to no movement in the arms or legs.

  • Breathing problems and distinctive horizontal eye movements from left to right are the defining characteristics of Pelizaeus-Merzbacher disease.

  • Tremors.

  • A lack of coordination and uncontrollable movements.

  • Weakness.

  • An unsteady walk and, over time, stiffness in the arms and legs are some additional symptoms.

Over time, muscle contractures frequently happen. The ability to think clearly may decline. Convulsions and skeletal distortion, such as scoliosis, can occur in some patients as a result of aberrant muscle stress on the bones.

How to Diagnose Pelizaeus-Merzbacher Disease?

  • A comprehensive physical examination, a thorough review of the patient's medical history, and a number of specialist tests, such as magnetic resonance imaging (MRI) to look for white matter deficiency, may all be used to make a diagnosis of Pelizaeus-Merzbacher disease.

  • Early detection of the severe types of Pelizaeus-Merzbacher disease may be facilitated by the identification of early myelination problems, such as a lack of myelination in the brainstem and cerebellum. A PLP1 gene test for molecular genetic confirmation of the diagnosis is available.

  • If a disease-causing mutation in the PLP1 gene has been found in an affected family member, carrier testing is an option.

  • If a PLP1 gene mutation is found in an affected family member, prenatal diagnostics and preimplantation genetic diagnosis are options.

How to Treat Pelizaeus-Merzbacher Disease?

Pelizaeus-Merzbacher illness is incurable. The goal of the treatment is to improve quality of life and may involve:

  • Medications that lessen seizures or muscle spasms.

  • Occupational or physical therapy to improve motor control, strength, and balance.

  • For the correction of uncontrollable eye movements, ocular therapies, including spectacles or surgery.

  • Counseling with a qualified mental health professional to improve coping mechanisms and manage the psychological impact of having a genetic disease.

The condition Pelizaeus-Merzbacher disease cannot be avoided. Consider genetic testing if one has Pelizaeus-Merzbacher disease or believes they could be a carrier for the condition. The gene mutation that causes the disease is searched for using a genetic test. One can better comprehend the test results, including the possibility of transferring PMD to the offspring, with the aid of a genetic counselor.


Depending on how severe the symptoms are, multiple outcomes are possible with Pelizaeus-Merzbacher disease. Usually, those with severe symptoms get worse over time, shortening life expectancy. However, other individuals may have a typical living pattern and only have minor symptoms that have little to no impact on their day-to-day activities. A doctor can explain how Pelizaeus-Merzbacher disease might affect one’s life or the life of their kid. One can better comprehend the test results, including the possibility of transferring Pelizaeus-Merzbacher disease to their offspring, with the aid of a genetic counselor. In order to formulate a treatment strategy that is effective, speak with a healthcare physician.


Last reviewed at:
31 Jan 2023  -  5 min read




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